The broad objective of this research program is a better understanding of the anatomical, biochemical, and physiological processes involved in the reactions of the cardiovascular and pulmonary systems to exercise. Experiments will be performed on the acute response and the chronic adaptation of these two systems to both dynamic and static exercise. The principal function of these combined systems (cardiovascular - pulmonary) is to furnish the required oxygen to the various tissues of the body. Thsu, our primary goal is to study quantitatively the mechanisms which regulate and limit the oxygen transport system in the body during exercise. However, these mechanisms must be viewed in the context of conditions regulating oxygen demand and utilization, particularly in skeletal muscle. Currently studies are being conducted at multiple levels including the integrated response to dynamic and static exercise in normal subjects and in patients with cardiovascular, pulmonary, neurological and metabolic diseases. Also, experiments are being performed in intact animals, isolated organs and tissues, and biochemical preparations in order to better understand the mechanisms involved in oxygen delivery and its proper distribution. Such a broad attack directed at all links in the oxygen transport system in the body should establish a better understanding of the determinants of human physical performance, provide a more sound basis for classification and quantitation of disease states affecting the cardiovascular and pulmonary systems, and may lead to more rational therapeutic methods. Close contact and cooperation between the members of the group primarily concerned with clinical research and applied physiology,and those who are working in the basic science areas of anatomy, biochemistry, and physiology have provided the background considered essential for the success of this program during the past 20 years. Such close relationships will provide an excellent environment for continued advancements in relation to responses and adaptations to exercise.